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B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene repertoire of B lymphocytes from germinal center-like foci in the synovial membrane indicates antigen selection.

Voswinkel J, Weisgerber K, Pfreundschuh M, Gause A - Arthritis Res. (2001)

Bottom Line: In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%).CDR3 were shorter and more variable in length than in RA.Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Universitätsklinikum Lübeck, Lübeck, Germany. Jvoswinkel@aol.com

ABSTRACT
The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM were stained for B and T lymphocytes. B cells were isolated from different areas of a focus. The rearranged VH genes were amplified by semi-nested polymerase chain reaction (PCR) using oligonucleotides specific for the six different VH families and heavy chain joining segments (JHs). PCR products were cloned and sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were potentially functional. Most of the rearranged genes were mutated (range, 1-15%). Thirty of 70 products had a mutational pattern typical for antigen selection. Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with data from healthy donors and patients with RA, while VH4 genes, in contrast to RA, were identified less frequently (10%) and VH5 genes were over-represented (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were shorter and more variable in length than in RA. Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

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Mutated nucleotide triplets and amino acid sequence of expanded B cell clones (a) VH1 and (b) VH3 in comparison with their respective gl gene (short tables). The amino acid position and the CDR positions are marked. Dashes indicate identity to the corresponding character on top. Amino acid replacements are indicated in the last line. (For whole sequences, see supplementary Figure 1.)
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Figure 3: Mutated nucleotide triplets and amino acid sequence of expanded B cell clones (a) VH1 and (b) VH3 in comparison with their respective gl gene (short tables). The amino acid position and the CDR positions are marked. Dashes indicate identity to the corresponding character on top. Amino acid replacements are indicated in the last line. (For whole sequences, see supplementary Figure 1.)

Mentions: Four of the VH1 products (F5-2c4, F5-3a4, F5-3b4 and 5c-4m6) deriving from different slides had an identically rearranged CDR3 and consecutively represent members of an expanding B lymphocyte clone (Fig. 3a). With 99% homology to DP21, they shared three mutations within the framework region (FR).


B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene repertoire of B lymphocytes from germinal center-like foci in the synovial membrane indicates antigen selection.

Voswinkel J, Weisgerber K, Pfreundschuh M, Gause A - Arthritis Res. (2001)

Mutated nucleotide triplets and amino acid sequence of expanded B cell clones (a) VH1 and (b) VH3 in comparison with their respective gl gene (short tables). The amino acid position and the CDR positions are marked. Dashes indicate identity to the corresponding character on top. Amino acid replacements are indicated in the last line. (For whole sequences, see supplementary Figure 1.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30712&req=5

Figure 3: Mutated nucleotide triplets and amino acid sequence of expanded B cell clones (a) VH1 and (b) VH3 in comparison with their respective gl gene (short tables). The amino acid position and the CDR positions are marked. Dashes indicate identity to the corresponding character on top. Amino acid replacements are indicated in the last line. (For whole sequences, see supplementary Figure 1.)
Mentions: Four of the VH1 products (F5-2c4, F5-3a4, F5-3b4 and 5c-4m6) deriving from different slides had an identically rearranged CDR3 and consecutively represent members of an expanding B lymphocyte clone (Fig. 3a). With 99% homology to DP21, they shared three mutations within the framework region (FR).

Bottom Line: In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%).CDR3 were shorter and more variable in length than in RA.Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Universitätsklinikum Lübeck, Lübeck, Germany. Jvoswinkel@aol.com

ABSTRACT
The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM were stained for B and T lymphocytes. B cells were isolated from different areas of a focus. The rearranged VH genes were amplified by semi-nested polymerase chain reaction (PCR) using oligonucleotides specific for the six different VH families and heavy chain joining segments (JHs). PCR products were cloned and sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were potentially functional. Most of the rearranged genes were mutated (range, 1-15%). Thirty of 70 products had a mutational pattern typical for antigen selection. Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with data from healthy donors and patients with RA, while VH4 genes, in contrast to RA, were identified less frequently (10%) and VH5 genes were over-represented (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were shorter and more variable in length than in RA. Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

Show MeSH
Related in: MedlinePlus